Therapeutic Targets of Triglyceride Metabolism as Informed by Human Genetics

详细信息    查看全文

• 作者：Robert C. Bauer¹ ; Sumeet A. Khetarpal¹ ; Nicholas J. Hand¹ ; Daniel J. Rader¹ ; ^{rader@mail.med.upenn.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：triglycerides ; genetics ; GWAS ; lipogenesis
• 刊名：Trends in Molecular Medicine
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：22
• 期：4
• 页码：328-340
• 全文大小：1819 K

文摘

Human genetics has contributed to the development of multiple drugs to treat hyperlipidemia and coronary artery disease (CAD), most recently including antibodies targeting PCSK9 to reduce LDL cholesterol. Despite these successes, a large burden of CAD remains. Genetic and epidemiological studies have suggested that circulating triglyceride (TG)-rich lipoproteins (TRLs) are a causal risk factor for CAD, presenting an opportunity for novel therapeutic strategies. We discuss recent unbiased human genetics testing, including genome-wide association studies (GWAS) and whole-genome or -exome sequencing, that have identified the lipoprotein lipase (LPL) and hepatic lipogenesis pathways as important mechanisms in the regulation of circulating TRLs. Further strengthening the causal relationship between TRLs and CAD, findings such as these may provide novel targets for much-needed potential therapeutic interventions.